Neoadjuvant chemo-immunotherapy with camrelizumab plus nab-paclitaxel and cisplatin in resectable locally advanced squamous cell carcinoma of the head and neck: a pilot phase II trial

Neoadjuvant chemoimmunotherapy has emerged as a potential treatment option for resectable head and neck squamous cell carcinoma (HNSCC). In this single-arm phase II trial (NCT04826679), patients with resectable locally advanced HNSCC (T2‒T4, N0‒N3b, M0) received neoadjuvant chemoimmunotherapy with camrelizumab (200 mg), nab-paclitaxel (260 mg/m2), and cisplatin (60 mg/m2) intravenously on day one of each three-week cycle for three cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included pathologic complete response (pCR), major pathologic response (MPR), two-year progression-free survival rate, two-year overall survival rate, and toxicities. Here, we report the perioperative outcomes; survival outcomes were not mature at the time of data analysis. Between April 19, 2021 and March 17, 2022, 48 patients were enrolled and received neoadjuvant therapy, 27 of whom proceeded to surgical resection and remaining 21 received non-surgical therapy. The ORR was 89.6% (95% CI: 80.9, 98.2) among 48 patients who completed neoadjuvant therapy. Of the 27 patients who underwent surgery, 17 (63.0%, 95% CI: 44.7, 81.2) achieved a MPR or pCR, with a pCR rate of 55.6% (95% CI: 36.8, 74.3). Treatment-related adverse events of grade 3 or 4 occurred in two patients. This study meets the primary endpoint showing potential efficacy of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin, with an acceptable safety profile, in patients with resectable locally advanced HNSCC.


Study design:
Single-center, single-arm, opened, phase II trial clinical study.

Intended number of patients:
48 patients.
Inclusion criteria: 1.The patient's pathological biopsy results must be confirmed to be squamous cell carcinoma of head and neck by pathologists.
4) Adequate coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤1.5 ULN; If patient is receiving anticoagulant therapy, it is acceptable that PT is in the prescribed anticoagulant range.
8. Female patients of reproductive age or male patients whose sexual partner is female patients of reproductive age shall use effective contraceptive measures throughout the treatment period until 6 months after the treatment period.
9. Sign written informed consent and be able to comply with the visits and related procedures specified in the program.
10. Can provide archived pathological tissues or fresh pathological tissues within 6 months for the detection of PD-L1 and other markers.

Exclusion criteria:
1. Patients were taking other investigational drugs at the same time.
2. Any treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibodies, or any other antibody or drug that specifically targets at T-cell costimulation or checkpoint pathways prior to study.
3. History of allergic reactions attributed to any monoclonal antibody or chemotherapy drug (paclitaxel, cisplatin) preparations or excipients.
4. Patients were also taking rifampicin, phenytoin sodium, carbamazepine, or barbiturates (these drugs induce CYP3A and may reduce plasma content of paclitaxel).

Received systemic therapy of Chinese herbal medicine with anti-tumor indications
or immunomodulatory drugs (including thymosin, interferon, interleukin, etc.) within 2 weeks prior to first administration.
6. Administration of a live, attenuated vaccine within 4 weeks prior to the first dose of treatment or planned for it during the study.
Note: Administration of inactivated virus vaccine for seasonal influenza is permitted within 4 weeks prior to the first dose of treatment, while live attenuated flu vaccines are not allowed.
7. Toxicity from prior antineoplastic therapy that did not return to grade 0 or 1 defined 12. HIV infection and carriers are known to exist (HIV antibody positive).
13. Severe infections that are in active period or clinically poorly controlled.
16. Any arterial thromboembolic event, including myocardial infarction, unstable angina, cardiocerebral events or transient ischemic attack (TIA), occurred within 6 months prior to enrollment.17.Significant malnutrition which need intravenous supplements while malnutrition corrected for over 4 weeks prior to first dose of the study was excluded.
18.A history of deep vein thrombosis, pulmonary embolism, or any other severe thromboembolism within 3 months prior to enrollment (Implantable Venous Access Port or duct-derived thrombosis, or superficial venous thrombosis is not considered as "severe" thromboembolism).
19. Uncontrolled metabolic disorders or other non-malignant organ or systemic diseases or secondary reactions to cancer that may result in higher medical risk and/or uncertainty in the assessment of survival.

SupplementaryFigure 1 2
Presentative images of pre and post-treatment assessments.CT images show an oropharyngeal patient with a CR (Pre: a; Post: b); while H&E images show an oral patient with a pCR (Pre: c; Post: d).Swimmer plot of progression-free survival (n=47

SupplementaryFigure 3 4 5 6
Distribution of TMB and PD-L1 expression level in patients with different anatomic sites (a and c) and TNM stages (b and d) analyzed by using the Kruskal-Wallis test.The dot represents an individual data point.The center line with a circle represents mean value, and the bar represents standard deviation.OC: Oral cancer(n=16); OPC: Oropharyngeal cancer (n=14); LC: Laryngeal cancer (n=9); HPC: Hypopharyngeal cancer (n=9); stage II (n=6); stage III (n=4); stage Iva (n=34); stage IVb (n=4); ns: No significance.Source data are provided as a Source Data file.Correlation analysis of radiographic tumor response with the density of tumorinfiltrating CD4+ T cells by using the Spearman correlation text (n=38; a).The baby-blue dot represents an individual data point.The line represents a fitted line.The grey shadow represents the corresponding 95% confidence interval.The multiplex immunofluorescence images of the tumor sites in patient 17 (b).Source data are provided as a Source Data file.Correlation analysis between radiographic tumor regression and TMB (n=47), PD-L1 expression (n=47), or density of tumor-infiltering immune cells (M2-like macrophage cells: n=47; S_M1-like macrophage cells: n=47; S_CD8+ T cells: n=47; S_M2-like macrophage cells: n=47; S_CD56bright cells: n=47; CD56dim cells: n=47; Tregs cells: n=38; S_CD56bright cells: n= 47; S_CD56dim cells: n=47; S_Tregs cells: n=39; S_CD4+ T cells: n=39) by using the Spearman correlation test.The baby-blue dot represents an individual data point.The line represents a fitted line of correlation.The grey shadow represents the corresponding 95% confidence interval.Source data are provided as a Source Data file.Comparisons of the density of tumor infiltration immune cells before and after neoadjuvant therapy in overall patients (n=19, a) and those with pCR (n=8, b) and non-pCR (n=11, c) using the paired Wilcoxon signed-rank test.The blue dot represents an individual data point of cell density at baseline, the red dot represents an individual data point after neoadjuvant therapy.The black line represents the direction of change in cell density following neoadjuvant therapy.*: p<0.05, ns: No significance.Source data are provided as a Source Data file.